Thread by @x2IndSpeculator

Finally, some reason & common sense in the official immunology.
"We describe several lines of evidence that argue AGAINST a direct impact of vaccine-induced memory T cells in PREVENTING symptomatic #SARSCoV2 INFECTION...
@fitterhappierAJ
nature.com/articles/s4157…

The contribution of T cell immunity in REDUCING the SEVERITY of infection, particularly with #SARS2 variants, REMAINS TO BE DETERMINED.
In reality protective immunity to most pathogens does not refer to a binary outcome (susceptible vs protected) but instead REFLECTS a SPECTRUM."

vs. INFECTION:
1) "To address the role of T cells in protection from #SARS2 infection is to identify contexts where T cell & nAb responses at least partially ‘decoupled’.
There is relatively little loss of T cell cross-reactivity to VoCs, including #Omicron. Thus, exposure of...

vaccinated to #SARS2 VoCs presents a situation in which T cell immunity SHOULD REMAIN largely INTACT, whereas effective concentrations of nAbs are reduced. Trials show that VE in preventing infection is REDUCED for these variants... despite the largely INTACT T cell recognition."

2) "Vaccination of previously infected individuals results in nAb levels severalfold higher than the levels observed after vaccination of naïve individuals. However, spike-specific T cell immunity does not appear to be similarly boosted, with spike-specific T cell frequencies...

comparable to those observed after vaccination of naïve individuals. Thus, if protection from infection tracked with T cells, then we might expect little difference in protection after vaccination of naïve or recovered individuals...

However, vaccination has been observed to have a significantly greater effectiveness in preventing infection in recovered individuals versus naïve individuals, which argues for a CRITICAL ROLE for nAbs."

3) "The potential for a COMPENSATORY increase in the number (and role) of some T cell responses in the absence of nAb responses, although the mechanisms of this are unclear. Importantly, this occurs in the context of B cell deficiency in the ‘priming’ stage of vaccination."

vs. SEVERE:
1) "we still find that nAb responses remain predictive of protection from severe disease & that the nAb titre associated with 50% protection from severe #SARS2 is 6x LOWER THAN the level REQUIRED to protect vs. infection (around 8 IU ml−1 versus 54 IU ml−1)...

Because of the lower levels of nAbs associated with protection from severe disease, this protection is expected to be sustained for MUCH LONGER than protection from acquisition of infection."

2) Viral clearance rates are significantly greater in vaccinated, with divergence occurring around day 6 after symptom onset...
a change in immune control occurring after clinical presentation may increase the viral clearance rate & contribute to protection from severe disease...

An analysis of the dynamics of immune recall early after breakthrough infection... shows RAPID RECALL of Ab responses occurring around day 5 after symptom onset (day 8 post-infection) but weak or no recall of CD4+ T cell & CD8+ T cell responses in blood around the same time...

3) "For example, geometric mean vaccine-induced nAb responses to the #Omicron variant compared with the ancestral strain are decreased more than tenfold (compared with a reduction of around 3.9-fold for the #Delta strain).

However, T cell responses to the #Omicron compared with the ancestral strain are reported to be decreased by a mean of ONLY 10–30% & are not significantly different between the #Delta strain & the #Omicron strain...

Two studies have shown reduced VE in preventing both symptomatic infection & hospitalization in the #Omicron-dominant period compared with the #Delta-dominant period, which appears consistent with the greater drop in nAb recognition of the #Omicron vs. the #Delta variant.

However, if immunity acts in a ‘two-step’ fashion, then reduced protection from hospitalization may, in part, be due to a higher number of symptomatic infections in vaccinated, while retaining the same level of protection from progression from symptomatic to severe disease."